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Molecular and Cellular Biology, November 1998, p. 6777-6783, Vol. 18, No. 11
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Involvement of CREB Binding Protein in Expression of Major Histocompatibility Complex Class II Genes via Interaction with the Class II Transactivator

Androniki Kretsovali,2 Theodora Agalioti,1,2 Charalambos Spilianakis,1,2 Eleni Tzortzakaki,1,2 Menie Merika,3 and Joseph Papamatheakis1,2,*

Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology,1 and Department of Biology, University of Crete,2 Heraklion, Crete, Greece, and Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 100323

Received 27 April 1998/Returned for modification 8 June 1998/Accepted 24 July 1998

The class II transactivator (CIITA) is a key regulatory factor that controls expression of the major histocompatibility complex (MHC) class II genes that are essential components for antigen presentation and thus regulation of the immune response. We show here that the adenovirus E1A protein interferes with the action of CIITA and inhibits both B-cell-specific and gamma interferon (IFN-gamma )-induced expression of MHC class II promoters. Transfection studies provide evidence for the functional role of the CREB-binding protein (CBP) in IFN-gamma and CIITA-mediated MHC class II promoter activation. We demonstrate that the N-terminally located transcription activation domain of CIITA physically interacts with both the N-terminal and the E1A-binding (C/H3) regions of CBP. These results suggest the involvement of a multisubunit complex, which contains the gene-specific coactivator CIITA and the versatile coactivator CBP, in MHC class II gene regulation, which may be responsible for both high-level expression and modulation by different signaling pathways.

* Corresponding author. Mailing address: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, P.O. Box 1527, Heraklion 711 10, Crete, Greece. Fax: 30 81 391101. Phone: 30 81 391100. E-mail: papamath{at}nefeli.imbb.forth.gr.

Molecular and Cellular Biology, November 1998, p. 6777-6783, Vol. 18, No. 11
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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